Spatially selective vagus nerve stimulation

ABSTRACT

By targeting on selected branches or fascicles of a vagus nerve using electrode placement and/or selection, one or more target branches of the vagus nerve are substantially activated by electrical stimulation pulses delivered to a branch without substantially activating one or more non-target branches. In one embodiment, vagus nerve stimulation is delivered through an electrode placed on a thoracic vagus nerve that is separated from a recurrent laryngeal nerve, such that the vagus nerve is stimulated without causing laryngeal muscle contractions. In another embodiment, vagus nerve stimulation is delivered through a multi-contact electrode with one or more contacts selected for delivering the electrical stimulation pulses to stimulate the vagus nerve without causing laryngeal muscle contractions.

CLAIM OF PRIORITY

This application claims the benefit of priority under 35 U.S.C. §119(e)of U.S. Provisional Patent Application Ser. No. 61/351,181, filed onJun. 3, 2010, which is herein incorporated by reference in its entirety.

TECHNICAL FIELD

This document relates generally to neurostimulation and moreparticularly to spatially selective vagus nerve stimulation forsubstantially activating one or more target nerve branches withoutsubstantially activating one or more non-target nerve branches.

BACKGROUND

Vagus nerve stimulation (VNS) has been applied to modulate variousphysiologic functions and treat various diseases. One example is themodulation of cardiac functions in a patient suffering heart failure ormyocardial infarction. The myocardium is innervated with sympathetic andparasympathetic nerves including the cardiac branches of the vagusnerve. Activities in the vagus nerve, including artificially appliedelectrical stimuli, modulate the heart rate and contractility (strengthof the myocardial contractions). Electrical stimulation applied to thevagus nerve is known to decrease the heart rate and the contractility,lengthening the systolic phase of a cardiac cycle, and shortening thediastolic phase of the cardiac cycle. This ability of VNS is utilized,for example, to control myocardial remodeling.

In addition to treating cardiac disorders such as myocardial remodeling,VNS is also known to be effective in treating disorders including, butnot limited to, depression, anorexia nervosa/eating disorders,pancreatic function, epilepsy, hypertension, inflammatory disease, anddiabetes. Because many physiological functions are controlled oraffected by the neural activities in the vagus nerve, there is a need tocontrol VNS for the desirable functional outcome while minimizing sideeffects.

SUMMARY

By targeting on selected branches or fascicles of a vagus nerve usingelectrode placement and/or selection, delivery of electrical stimulationpulses is controlled to substantially activate one or more targetbranches of the vagus nerve without substantially activating one or morenon-target branches.

In one embodiment, electrical stimulation pulses are delivered to anelectrode placed on or adjacent to a first branch of the vagus nerve.The first branch is separate from a second branch of the vagus nerve andselected to allow for substantial activation of one or more targetbranches of the vagus nerve by the electrical stimulation pulses withoutsubstantially activating the second branch.

In one embodiment, electrical stimulation pulses are delivered to anelectrode placed on a portion of a cervical vagus nerve trunk or aportion of a thoracic vagus nerve (tVN). The delivery of the electricalstimulation pulses is controlled such that one or more target branchesof the vagus nerve are activated by the electrical stimulation pulseswithout causing contraction of a laryngeal muscle innervated by arecurrent laryngeal nerve (RLN).

In one embodiment, a system for stimulating the vagus nerve includes anelectrode, a neural sensing circuit, a myoelectric sensing circuit, anda neurostimulator. The electrode is placed on a first branch of thevagus nerve to allow for delivery of electrical stimulation pulses tothe first branch. The neural sensing circuit senses a stimulation-evokedelectroneurographic (ENG) signal representative of a response of thevagus nerve to the electrical stimulation pulses. The myoelectricsensing circuit senses a stimulation-evoked electromyographic (EMG)signal representative of a response of a muscle to the electricalstimulation pulses, the muscle innervated by a second branch of thevagus nerve. The neurostimulator includes a stimulation circuit and astimulation control circuit. The stimulation circuit delivers theelectrical stimulation pulses to the first branch through the electrode.The stimulation control circuit controls the delivery of the electricalstimulation pulses using a plurality of stimulation parameters andincludes a parameter adjuster that allows for adjustment of one or morestimulation parameters of the plurality of stimulation parameters usingthe ENG signal and the EMG signal.

This Summary is an overview of some of the teachings of the presentapplication and not intended to be an exclusive or exhaustive treatmentof the present subject matter. Further details about the present subjectmatter are found in the detailed description and appended claims. Otheraspects of the invention will be apparent to persons skilled in the artupon reading and understanding the following detailed description andviewing the drawings that form a part thereof. The scope of the presentinvention is defined by the appended claims and their legal equivalents.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings illustrate generally, by way of example, variousembodiments discussed in the present document. The drawings are forillustrative purposes only and may not be to scale.

FIG. 1 is an illustration of an embodiment of a vagus nerve stimulation(VNS) system and portions of an environment in which the VNS system isused.

FIG. 2 is a block diagram illustrating an embodiment of an electrode anda neurostimulator of the VNS system.

FIG. 3 is a flow chart illustrating an embodiment of a method ofspatially selective VNS.

FIG. 4 is a flow chart illustrating another embodiment of a method ofspatially selective VNS.

FIG. 5 is an illustration of a system for testing the method of FIG. 4.

FIGS. 6A and 6B are illustrations of results of testing the method ofFIG. 4.

FIG. 7 is a flow chart illustrating an embodiment of another method ofspatially selective VNS.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings which form a part hereof, and in which is shown byway of illustration specific embodiments in which the invention may bepracticed. These embodiments are described in sufficient detail toenable those skilled in the art to practice the invention, and it is tobe understood that the embodiments may be combined, or that otherembodiments may be utilized and that structural, logical and electricalchanges may be made without departing from the spirit and scope of thepresent invention. The following detailed description provides examples,and the scope of the present invention is defined by the appended claimsand their legal equivalents.

It should be noted that references to “an”, “one”, or “various”embodiments in this disclosure are not necessarily to the sameembodiment, and such references contemplate more than one embodiment.

This document discusses a method and system for stimulating the vagusnerve to modulate one or more target functions while minimizingstimulation-evoked side effects. Vagus nerve stimulation (VNS) has beenused for the treatment of neurological disorders including depressionand epilepsy. VNS is also investigated for treatment of variousdisorders such as Alzheimer's disease, anxiety, heart failure, andobesity.

The vagus nerve originates in the medulla and targets multiple organs ina person's body through a complex functional innervation pattern. Thereare both efferent and afferent nerve fibers within the vagus nerve trunkthat convey neural activities to and from visceral organs such as theesophagus, gastrointestinal tract, kidney and pancreas (abdominal branchof vagus), thoracic organs such as the heart and lungs (thoracic branchof vagus), and voluntary muscles of the neck and multiple segments ofthe upper airway (recurrent laryngeal nerve, RLN). Such complexity hasbeen significantly limiting the effectiveness of VNS and the overallpatient population that may benefit from this therapy.

The difficulty in therapeutic application of VNS is further complicatedby the total number of fibers within the vagus nerve trunk and thedistribution of nerve fibers having different diameter. In an adult dog,which has been used as an animal model for the human vagus nerve, thecervical vagus nerve trunk contains approximately 20,000 myelinatedneurons and an even greater number of unmyelinated neurons. Both thehuman and canine vagus nerves also share a common classification schemedefined by the diameter of nerve fibers. This is based on the classicaldesignation of A (myelinated), B (myelinated parasympathetic) and C(unmyelinated) type fibers, as summarized in Table 1.

TABLE 1 Summary of Vagus Nerve Fiber Type Properties. A-Fibers B-FibersC-Fibers Diameter (μm)   5-20     1-3   0.2-2   Myelinated Yes Yes NoConduction Velocity (m/s)   30-120    3-20  0.3-2   Per-Unit Latencies(ms/cm) 0.08-0.3  0.5-3.3   5-33.3

Currently, a typical site of electrode implantation for VNS therapy isat the cervical spinal level between the thyroid cartilage and thesternum of the patient. At this location, the vagus nerve contains awide array of nerve fibers, as summarized in Table 1. As a result,stimulation parameters used for VNS therapy are largely determined bytitrating the various temporal properties of the electrical pulses(e.g., amplitude, frequency, duty cycle). Various studies applying VNSto animal models and human patients led to the establishment ofrecommended clinical parameters for antiepileptic and other applicationsof VNS. However, stimulation-evoked side effects, such as voicehoarseness, coughing, and pain, remain a problem in applying VNStherapy. These unwanted effects of VNS result from (1) the reversedrecruitment order of myelinated nerve fibers during electricalstimulation (i.e., lower activation threshold for larger diameterfibers) and (2) the vast majority of larger diameter fibers within thevagus nerve innervate the voice box and upper airway via the RLN.Delivering electrical stimulation to the vagus nerve through bipolarhelical nerve cuff electrode, for example, is known to result innon-selective activation of all nerve fibers within the nerve trunk, andhence little control over unintended generation of side-effectsincluding unintended laryngeal activities.

The present method and system provide for spatially selective activationof vagus nerve branches to maximize overall therapeutic efficacy of VNS.In this document, “spatially selective activation of vagus nervebranches” refers to activation of one or more selected (or specified)vagus nerve branches by delivering electrical stimulation to a space,such as a particular segment or branch of the vagus nerve, identified toallow for activation of the one or more selected vagus nerve brancheswithout causing an unwanted side effect such as activated of anon-selected vagus nerve branch. By targeting on selected branches orfascicles of the vagus nerve using electrode placement and/or selection,the electrical stimulation is delivered to activate one or more targetnerve pathways while minimizing activation of one or more non-targetnerve pathways associated with stimulation-evoked side effects. In oneembodiment, VNS is delivered to a thoracic vagus nerve (tVN) in alocation separate from the RLN to allow placement of an electrode on thetVN but isolated from the RLN, such that the delivery of the electricalstimulation through this electrode results in desirable modulation ofcardiovascular functions without evoking unwanted laryngeal activities.Surgical separation of a portion of the tVN from the RLN may be requiredto create adequate space for such electrode placement. In anotherembodiment, the topographical organization of the nerve fascicles of thecervical vagus nerve trunk allows target selection using a singlemulti-contact nerve electrode. The contacts in the nerve electrode areselected for delivering VNS to result in the desirable modulation ofcardiovascular functions without evoking the unwanted side effectscaused by activation of one or more non-targeted fibers of the vagusnerve. While efferent laryngeal muscle contraction is discussed as aspecific example of the unwanted side effects to be avoided using thepresent method and system, the present subject matter applies to controlof unwanted side effects by spatially selective activation of vagusnerve branches. Another example of such unwanted side effects to beavoided using the present method and system includes airway reflexesevoked by (1) direct activation of afferent RLN fibers and/or (2)indirect activation of afferent RLN activity generated by efferentlaryngeal muscle contractions.

FIG. 1 is an illustration of an embodiment of a VNS system 100 andportions of an environment in which system 100 is used. FIG. 1 shows aportion of a vagus nerve 101 having segments or branches including acervical vagus nerve trunk 102, a tVN 104, and an RLN 106. In theillustrated embodiment, the physical separation between tVN 104 and RLN106 after they diverge from cervical vagus nerve trunk 102 allowsplacement of a stimulation electrode 136 on tVN 104. Electrode 136allows for delivery of VNS to tVN 104, which innervates thoracic organs,including a heart 105, and abdominal organs through further branches ofthe vagus nerve, without activating the RLN, which innervates laryngealmuscles (represented in FIG. 1 by a laryngeal muscle 107). The physicalseparation between tVN 104 and RLN 106 may be created or partiallycreated by surgery to allow for proper placement of electrode 136without affecting neural conduction within these nerve branches. In oneembodiment, tVN 104 and RLN 106 are longitudinally separated bydissecting the portion of the vagus nerve trunk including these twobranches to the location where fibers of tVN 104 and RLN 106 diverge, atapproximately the level of the subclavian artery. In one embodiment,electrode 136 is placed on tVN 104 within about one centimeter from thelocation where tVN 104 and RLN 106 diverge.

While the application involving tVN 104 and RLN 106 as illustrated inFIG. 1 is discussed as a specific example in this document, the presentmethod may apply to other branches of the vagus nerve or other nervesbeing targets of neurostimulation. In various embodiments, a portion ofa nerve trunk such as a vagus nerve trunk including a first branch and asecond branch is dissected to separate the first and second branches.The first branch controls one or more physiological functions of apatient. The second branch controls one or more other physiologicalfunctions of the patient. The first branch includes the stimulation siteto which the electrical stimulation is delivered. The second branch is anon-target branch that is not intended to be activated by the electricalstimulation pulses. The one or more target branches, which include butare not limited to the first branch, are intended to be activated by theelectrical stimulation. The stimulation electrode is placed on the firstbranch to allow for delivery of electrical stimulation to activate oneor more target branches of the nerve trunk (including the first branch)without activating the second branch.

In the illustrated embodiment, system 100 includes an implantablemedical device 110 electrically coupled to electrode 136 through animplantable lead 130. Implantable medical device 110 includes aneurostimulator 120 encapsulated by an implantable housing 112, and aheader 114 attached to implantable housing 112 and providing forconnection to lead 130. Neurostimulator 120 is discussed below withreference to FIG. 2. In one embodiment, implantable medical device 110is a neurostimulator. In other embodiments, in addition toneurostimulator 120, implantable medical device 110 includes one or moreof a cardiac pacemaker, a cardioverter/defibrillator, a drug deliverydevice, a biologic therapy device, and any other monitoring ortherapeutic devices. In the illustrated embodiment, lead 130 includes aproximal end 132, a distal end 133, and an elongate body 131 coupledbetween proximal end 132 and distal end 133. Proximal end 132 isconfigured to be connected to implantable medical device 110. Distal end133 includes, or is otherwise coupled to, electrode 136. Electrode 136is a bipolar nerve cuff electrode. In another embodiment, electrode 136is a monopolar nerve cuff electrode, and another electrode such as aportion of implantable housing 112 is used. In various embodiments,electrode 136 includes any form of electrode that allows for activationof tVN 104 by electrical stimulation delivered from neurostimulator 120.

While FIG. 1 illustrates the embodiment in which the placement ofelectrode 136 on tVN 104 allows for VNS to modulate cardiovascularfunctions without evoking unwanted laryngeal activities, the presentsubject matter generally includes selective activation of vagus nervebranches by selecting the sites to which the electrical stimulationpulses are delivered through multiple electrodes or a multi-contactelectrode. For example, a multi-contact electrode may be placed incervical vagus nerve trunk 102, cranial to the location where tVN 104and RLN 106 diverge. Stimulation is delivered through variouscombination of contacts of the multi-contact electrode to select one ormore contacts allowing for the VNS to substantially activate tVN 104without substantially activating RLN 106.

FIG. 2 is a block diagram illustrating an embodiment of an electrode 236and a neurostimulator 220. Electrode 236 represents an embodiment ofelectrode 136. Neurostimulator 220 represents an embodiment ofneurostimulator 120.

Neurostimulator 220 includes a stimulation circuit 240 and a stimulationcontrol circuit 242. Stimulation circuit 240 produces electricalstimulation pulses and delivers the electrical stimulation pulses toelectrode 236. Stimulation control circuit 242 controls the delivery ofthe electrical stimulation pulses using a plurality of stimulationparameters and includes a parameter adjuster 244 and a storage circuit246. Parameter adjuster 244 allows for adjustment of one or morestimulation parameters of the plurality of stimulation parameters suchthat the intensity of the electrical stimulation pulses is provided forsubstantially activating one or more target branches of a nerve such asthe vagus nerve without substantially activating one or more non-targetbranches of the nerve. In one embodiment, the plurality of stimulationparameters includes pulse amplitude, pulse width, pulse frequency, dutycycle, cycle unit, and stimulation duration. The pulse amplitude is theamplitude of each electrical stimulation pulse specified as voltage(e.g., for constant-voltage pulse) or current (e.g., forconstant-current pulse). The pulse width is the duration of eachelectrical stimulation pulse. The pulse frequency is the frequency atwhich the electrical stimulation pulses are delivered and may also bespecified as an inter-pulse interval being the time interval betweensuccessive pulses. The duty cycle is the ratio of a stimulation intervalto the cycle unit. The electrical stimulation pulses are deliveredduring only the stimulation interval. The stimulation duration is theduration of a delivery of neurostimulation therapy. The cycle unit andthe stimulation durations may be specified by time or number of pulses,and the duty cycles may be specified by time or number of pulses in eachcycle unit. For example, “pulses delivered at a pulse frequency of 20 Hzat a duty cycle of 10% and a unit cycle of 1 second” is equivalent to“pulses delivered at a pulse frequency of 20 Hz at a duty cycle of 2pulses per unit cycle of 20 pulses”.

Storage circuit 246 stores values for the plurality of stimulationparameters. In one embodiment, storage circuit 246 stores values of theone or more stimulation parameters selected to substantially activatethe one or more target branches of the nerve without substantiallyactivating the one or more non-target branches of the nerve. In oneembodiment, a value of the pulse amplitude is selected to substantiallyactivate the one or more target branches of the nerve withoutsubstantially activating the one or more non-target branches of thenerve, and stored in storage circuit 246.

In various embodiments, the circuit of neurostimulator 220, includingits various elements discussed in this document, is implemented using acombination of hardware and software. In various embodiments,stimulation control circuit 242 may be implemented using anapplication-specific circuit constructed to perform one or moreparticular functions or a general-purpose circuit programmed to performsuch function(s). Such a general-purpose circuit includes, but is notlimited to, a microprocessor or a portion thereof, a microcontroller orportions thereof, and a programmable logic circuit or a portion thereof.

FIG. 3 is a flow chart illustrating an embodiment of a method 300 ofspatially selective VNS. In one embodiment, method 300 is performedusing system 100 including its embodiments discussed in this document.

At 310, if necessary for electrode placement, a portion of the vagusnerve including a first branch and a second branch is longitudinallydissected and separated, without damaging the normal neural conductionin these branches. At 320, an electrode, such as a nerve cuff electrode,is placed on or adjacent to the first branch.

At 330, electrical stimulation pulses are delivered to the first branchthrough the electrode placed on the first branch. At 340, the deliveryof the electrical stimulation pulses is controlled to substantiallyactivate one or more target branches of the vagus nerve, including thefirst branch, without substantially activating the second branch. Thisincludes adjusting one or more stimulation parameters controlling theintensity of the electrical stimulation pulses. In one embodiment, theone or more stimulation parameters are determined by monitoring neuralsignals and/or myoelectric signals indicative of the activation of theone or more target branches and the second branch. Surgical separationat 310 is not necessary if the electrode can be placed on or adjacent tothe first branch to allow substantial activation of the one or moretarget branches of the vagus nerve, including the first branch, withoutsubstantially activating the second branch. In this document,substantially activating a nerve means causing a detectablestimulation-evoked neural response. Such stimulation-evoked neuralresponse may be detected, for example, by sensing neural traffic in thenerve and/or sensing a signal indicative of a physiological functionmodulated by the neural traffic.

FIG. 4 is a flow chart illustrating an embodiment of a method 400 ofspatially selective VNS. Method 400 includes an embodiment of method 300with the first branch of the vagus nerve being tVN 104 and the secondbranch of the vagus nerve being RLN 106. In one embodiment, method 400is performed using system 100 including its embodiments discussed inthis document.

At 410, electrical stimulation pulses are delivered to tVN 104, whichhas been longitudinally separated from RLN 106. At 420, the intensity ofthe electrical stimulation pulses is controlled for substantiallyactivating one or more target branches of the vagus nerve withoutcausing contraction of a laryngeal muscle that is innervated by RLN 106.

In one embodiment, this intensity is determined by sensing signalsrepresentative and/or indicative of the neural responses to the deliveryof the stimulation pulses. For example, a stimulation-evokedelectroneurographic (ENG) signal representative of a response of thecervical vagus nerve trunk to the electrical stimulation pulses issensed, and a stimulation-evoked electromyographic (EMG) indicative ofthe response of the RLN to the electrical stimulation pulses is sensed.The one or more target branches of the vagus nerve are considered to besubstantially activated when the amplitude of the ENG signal exceeds aspecified ENG threshold. The contraction of a laryngeal muscle is notconsidered to be occurring, or the RLN is not considered to beactivated, when the amplitude of the EMG signal does not exceed aspecified EMG threshold. In one embodiment, the intensity of theelectrical stimulation pulses is determined by adjusting the pulseamplitude and/or the pulse width and observing the effect of theadjustment on the amplitude of the ENG signal and the amplitude of theEMG signal.

FIG. 5 is an illustration of a system 500 for testing method 400. Thevagus nerve 101 is dissected distally to approximately the level of thesubclavian artery where multiple branches of the vagus nerve trunk canbe separated and identified. RLN 106 and the remaining part of the vagusnerve (tVN 104) are isolated and instrumented with individual nerve cuffelectrodes 538 (on or adjacent to RLN 106) and 536 (on or adjacent totVN 104). A tripolar nerve cuff electrode 566 is implanted on cervicalvagus nerve trunk 102 to record antidromic ENG activity, and anelectrode 556 including a pair of insulated stainless steel wires wasinserted into laryngeal muscle 107 (e.g., the posterior cricoarytenoidmuscle) to measure laryngeal EMG.

A first neurostimulator 520A is electrically connected to electrode 536to deliver electrical stimulation pulses to tVN 104. A secondneurostimulator 520B is electrically connected to electrode 538 todeliver electrical stimulation pulses to RLN 106. An example for each offirst neurostimulator 520A and second neurostimulator 520B isneurostimulator 220 as discussed above. For the purpose of the test,first neurostimulator 520A and second neurostimulator 520B may includeone device being used as first neurostimulator 520A and secondneurostimulator 520B at different times, or two devices that can be usedconcurrently or at different times. First neurostimulator 520A andsecond neurostimulator 520B may each be an implantable device or anexternal device that is electrically coupled to the correspondingelectrode via an implantable or percutaneous lead. A neural sensingcircuit 560 is electrically coupled to electrode 566 and senses astimulation-evoked ENG signal representative of a response of cervicalvagus nerve trunk 102 to the electrical stimulation pulses delivered totVN 104 and the electrical stimulation pulses delivered to RLN 106. AnENG parameter producer 562 produces an amplitude of the ENG signalindicative of the response of cervical vagus nerve trunk 102 using thesensed ENG signal. A myoelectric sensing circuit 550 is electricallycoupled to electrode 556 and senses a stimulation-evoked EMG signalindicative of the response to the electrical stimulation pulsesdelivered to tVN 104 and the electrical stimulation pulses delivered toRLN 106. An EMG parameter producer 552 produces an amplitude of the EMGsignal indicative of the response of the laryngeal muscle using thesensed EMG signal.

FIGS. 6A and 6B are illustrations of results of testing method 400. Thefeasibility of selectively activating individual branches of the vagusnerve was investigated using a canine model and system 500. FIGS. 6A and6B show recruitment curves obtained by recording the stimulation-evokedENG and EMG activities, which demonstrates a clear separation of nervesinnervating the larynx from those of the vagus nerve that continueddistally into the thorax. FIG. 6A shows that during selective RLNstimulation (through electrode 538), the concomitant activation oflow-threshold A-fibers (current=0.5 mA) and laryngeal EMG activityindicates a strong correlation between these large diameter fibers andmuscles of the larynx. In contrast, FIG. 6B shows that selectivestimulation of the tVN (through electrode 536, for which a monopolarnerve cuff electrode was used) has a significantly higher threshold foractivating ENG activity (current=2 mA), which reaches a plateau atapproximately 4 mA. The activation of laryngeal EMG activity above 4 mAindicates that the threshold at which the tVN stimulation current spillsover into the adjacent RLN branch, thus indicating a need to adjuststimulation intensity.

These results show that the anatomical divergence of multiple branchesof the vagus nerve allows for selectively stimulating specific subsetsof nerves within the vagus nerve to achieve desirable therapeuticeffects while minimizing side-effects. The topographical organization ofthe nerve fascicles also allows for use of a single multi-contact nerveelectrode as the neural interface for an implanted device.

In various embodiments, spatially selective VNS is applied by selectinga stimulation site on a specific nerve branch and a stimulationintensity to substantially activate the one or more target branches ofthe vagus nerve without substantially activating one or more non-targetbranches of the vagus nerve. A nerve is substantially activated when thestimulation-evoked neural response is detectable (such as when theamplitude of an ENG signal is at or above a specified ENG threshold) orwhen a stimulation-evoked response being a physiological functioncontrolled by the nerve is detectable (such as when the amplitude of theEMG signal is at or above a specified EMG threshold). Likewise, a nerveis not substantially activated when the stimulation-evoked neuralresponse is not detectable (such as when the amplitude of an ENG signalis below a specified ENG threshold) or when a stimulation-evokedresponse being a physiological function controlled by the nerve isdetectable (such as when the amplitude of the EMG signal is below aspecified EMG threshold).

FIG. 7 is a flow chart illustrating an embodiment of a method 700 ofspatially selective VNS. In one embodiment, method 700 is performedusing system 100 including its embodiments discussed in this document,with electrode 136 being a multi-contact electrode.

At 710, a multi-contact electrode is placed on cervical vagus nervetrunk 102 cranial to the location where tVN 104 and RLN 106 diverge. Thecontacts of the multi-contact electrode are distributed to allowselective stimulation of the fascicles of cervical vagus nerve trunk102. At 720, one or more contacts of the multi-contact electrode areselected for substantially activating one or more target branches of thevagus nerve without causing contraction of a laryngeal muscle that isinnervated by RLN 106. Electrical stimulation pulses are deliveredthrough various contacts or combination of contacts to identify the oneor more contacts to be selected. Stimulation control circuit 242controls the delivery of the electrical stimulation pulses using theplurality of stimulation parameters including one or more stimulationparameters specifying the selection of the one or more contacts of themulti-contact electrode. Parameter adjuster 244 adjusts the one or morestimulation parameters during the process of selecting the one or morecontacts. The one or more stimulation parameters specifying the one ormore contact selected at completion of this process are stored instorage circuit 246 for the subsequent VNS therapy.

In one embodiment, the electrical stimulation pulses are delivered usingat least two contacts of the multi-contact electrode used as a bipolarelectrode. In another embodiment, the electrical stimulation pulses aredelivered using at least one contact of the multi-contact electrode usedas a monopolar electrode and a separate electrode.

In one embodiment, this process of selecting the one or more contactsincludes sensing signals representative and/or indicative of the neuralresponses to the delivery of the stimulation pulses. For example, astimulation-evoked electroneurographic (ENG) signal representative of aresponse of the cervical vagus nerve trunk to the electrical stimulationpulses is sensed, and a stimulation-evoked electromyographic (EMG)indicative of the response of the RLN to the electrical stimulationpulses is sensed. The one or more target branches of the vagus nerve areconsidered to be substantially activated when the amplitude of the ENGsignal exceeds a specified ENG threshold. The contraction of a laryngealmuscle is not considered to be occurring, or the RLN is not consideredto be activated, when the amplitude of the EMG signal does not exceed aspecified EMG threshold. In one embodiment, the process of selecting theone or more contacts includes sweeping through various contacts and/orcombination of contacts of the multi-contact electrode and observing theeffect of the adjustment on the amplitude of the ENG signal and theamplitude of the EMG signal.

It is to be understood that the above detailed description is intendedto be illustrative, and not restrictive. Other embodiments will beapparent to those of skill in the art upon reading and understanding theabove description. The scope of the invention should, therefore, bedetermined with reference to the appended claims, along with the fullscope of equivalents to which such claims are entitled.

1. A method for electrically stimulating a vagus nerve in a living body,the method comprising: delivering electrical stimulation pulses to anelectrode placed on or adjacent to a first branch of the vagus nerve,the first branch separate from a second branch of the vagus nerve andselected to allow for substantial activation of one or more targetbranches of the vagus nerve by the electrical stimulation pulses withoutsubstantially activating the second branch.
 2. The method of claim 1,wherein delivering the electrical stimulation pulses to the electrodecomprises delivering the electrical stimulation pulses from animplantable medical device through an implantable lead coupled to theimplantable medical device and including or coupled to the electrode. 3.The method of claim 2, wherein delivering the electrical stimulationpulses to the electrode comprises delivering the electrical stimulationpulses to a cuff electrode.
 4. The method of claim 1, wherein the firstbranch is a thoracic vagus nerve (tVN), and the second branch is arecurrent laryngeal nerve (RLN).
 5. The method of claim 4, comprisingcontrolling one or more cardiovascular functions by adjusting one ormore stimulation parameters controlling the activation of the one ormore target branches of the vagus nerve by the electrical stimulationpulses.
 6. The method of claim 4, comprising: sensing astimulation-evoked electroneurographic (ENG) signal representative of aresponse of the one or more target branches to the electricalstimulation pulses; sensing a stimulation-evoked electromyographic (EMG)signal representative of a response of a laryngeal muscle to theelectrical stimulation pulses; and controlling an intensity of theelectrical stimulation pulses using an amplitude of the ENG signal andan amplitude of the EMG signal.
 7. A method for electrically stimulatinga vagus nerve in a living body, the method comprising: deliveringelectrical stimulation pulses to an electrode placed on a portion of acervical vagus nerve trunk or a portion of a thoracic vagus nerve (tVN);and controlling the delivery of the electrical stimulation pulses suchthat one or more target branches of the vagus nerve are activated by theelectrical stimulation pulses without causing contraction of a laryngealmuscle innervated by a recurrent laryngeal nerve (RLN).
 8. The method ofclaim 7, comprising: delivering the electrical stimulation pulses to theelectrode placed on the portion of the tVN; and controlling an intensityof the electrical stimulation pulses such that the one or more targetbranches of the vagus nerve are activated by the electrical stimulationpulses without causing the contraction of the laryngeal muscleinnervated by the RLN.
 9. The method of claim 8, wherein controlling theintensity of the electrical stimulation pulses comprises adjusting apulse amplitude of the electrical stimulation pulses.
 10. The method ofclaim 7, comprising: delivering the electrical stimulation pulses to amulti-contact electrode placed on the portion of the cervical vagusnerve trunk; and selecting one or more contacts of the multi-contactelectrode for delivering the electrical stimulation pulses such that theone or more target branches of the vagus nerve are activated by theelectrical stimulation pulses without causing the contraction of thelaryngeal muscle innervated by the RLN.
 11. The method of claim 7,comprising: sensing a stimulation-evoked electroneurographic (ENG)signal representative of a response of the cervical vagus nerve trunk tothe electrical stimulation pulses; and sensing a stimulation-evokedelectromyographic (EMG) signal representative of the response of thelaryngeal muscle to the electrical stimulation pulses.
 12. The method ofclaim 11, comprising determining one or more stimulation parameterscontrolling the delivery of the electrical stimulation pulses using theENG signal and the EMG signal.
 13. The method of claim 12, whereindetermining the one or more stimulation parameters comprises determiningthe one or more stimulation parameters to result in an amplitude of theENG signal exceeding a specified ENG threshold and an amplitude of theEMG signal below a specified EMG threshold.
 14. The method of claim 7,wherein delivering the electrical stimulation pulses to the electrodecomprises delivering the electrical stimulation pulses from animplantable medical device to the electrode through an implantable leadcoupled between the implantable medical device and the electrode. 15.The method of claim 14, wherein delivering the electrical stimulationpulses to the electrode comprises delivering the electrical stimulationpulses to a cuff electrode configured to be placed on the tVN.
 16. Themethod of claim 14, comprising controlling the delivering the electricalstimulation pulses using one or more stimulation parameters selected forcontrolling a cardiovascular function.
 17. The method of claim 14,comprising controlling the delivering the electrical stimulation pulsesusing one or more stimulation parameters selected for treating anabnormal cardiovascular condition.
 18. A system for stimulating thevagus nerve having multiple branches, the system comprising: anelectrode configured to be placed on a first branch of the vagus nerveto allow for delivery of electrical stimulation pulses to the firstbranch; a neural sensing circuit configured to sense astimulation-evoked electroneurographic (ENG) signal representative of aresponse of the vagus nerve to the electrical stimulation pulses; amyoelectric sensing circuit configured to sense a stimulation-evokedelectromyographic (EMG) signal representative of a response of a muscleto the electrical stimulation pulses, the muscle innervated by a secondbranch of the vagus nerve; a neurostimulator including: a firststimulation circuit configured to deliver the electrical stimulationpulses to the first branch through the electrode; and a stimulationcontrol circuit configured to control the delivery of the electricalstimulation pulses using a plurality of stimulation parameters, thestimulation control circuit including a parameter adjuster configure toallow adjustment of one or more stimulation parameters of the pluralityof stimulation parameters using the ENG signal and the EMG signal. 19.The system of claim 18, wherein the electrode comprises a cuffelectrode.
 20. The system of claim 19, wherein the stimulation controlcircuit comprises a storage circuit storing the one or more stimulationparameters adjusted for an amplitude of the ENG signal exceeding aspecified ENG threshold and an amplitude of the EMG signal below aspecified EMG threshold.